Objective The objective of this real-world study was to quantify and project the cumulative incidence of atrial fibrillation (AF) associated with exposure to ivabradine (IVB) in naïve-AF heart failure (HF) patients.

Methods A retrospective observational comparative study was performed using a health plan claims database. The new diagnosis of AF was compared between adult HF patients receiving IVB versus no IVB controls (CTRs) over 180-day follow-up period. Eligible IVB subjects were free from AF diagnosis before the IVB index date, which should be longer than 6 months. Incidence-density sampling was performed to select matched CTRs based on clinical characteristics, AF naïve status and time to be selected as a CTRs corresponding to the time to receive IVB from the initial HF diagnosis. The measure of IVB-AF association was tested using Cox Proportional Hazards Regression model.

Results Of the 153 IVB and 4,494,305 CTRs meeting the AF-naïve HF status, the analytic cohort of 107 IVB and 321 matched controls were created. The groups were well matched for age: 52.9±11.3 (IVB) vs. 53.5±11.8, gender: 57% male, HFrEF diagnosis: 66.4%, co-morbidities: hypertension 81.3% and coronary artery disease event 38.3%, and goal-directed medical therapy: ß-adrenergic blockers 89.7%, ACEi/ARB/sacubitril/valsartan 79.4%, mineral corticoid antagonists 39.3%. The adjusted HR [95% CI] estimates was 7.293 [4.985-10.668]. The only variable that predicted AF incidence was the IVB prescription.

Conclusions In HF AF-naive patients, analysis of healthcare claims point to a significant risk of AF receiving IVB.

The authors have declared no competing interest.

This study is a database trial using a de-identified health plan claims database.

University of Utah Cardiovascular Clinical Pharmacology Research Fund.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Using the database was deemed exempt from the human subject research review by the University of Illinois Chicago Institutional Review Board.

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Author Disclosures: The authors have no disclosures with the content of this manuscript.

Conflict of Interest: The authors have no conflict of interest associated with the content of this manuscript.

Funding: University of Utah Cardiovascular Clinical Pharmacology Research Fund.

All data will be available through the corresponding author upon request.